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Electrochemical nitrate (NO3 - ) reduction reaction (NO3 - RR) is a potential sustainable route for large-scale ambient ammonia (NH3 ) synthesis and regulating the nitrogen cycle. However, as this reaction involves multi-electron transfer steps, it urgently needs efficient electrocatalysts on promoting NH3 selectivity. Herein, a rational design of Co nanoparticles anchored on TiO2 nanobelt array on titanium plate (Co@TiO2 /TP) is presented as a high-efficiency electrocatalyst for NO3 - RR. Density theory calculations demonstrate that the constructed Schottky heterostructures coupling metallic Co with semiconductor TiO2 develop a built-in electric field, which can accelerate the rate determining step and facilitate NO3 - adsorption, ensuring the selective conversion to NH3 . Expectantly, the Co@TiO2 /TP electrocatalyst attains an excellent Faradaic efficiency of 96.7% and a high NH3 yield of 800.0 µmol h-1 cm-2 under neutral solution. More importantly, Co@TiO2 /TP heterostructure catalyst also presents a remarkable stability in 50-h electrolysis test.
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Iodide (I-) is crucial to thyroid function, and its regulation in thyrocytes involves ion transporters and reactive oxygen species (ROS). However, the extent of 2Cl-/H+ exchanger (ClC-3) involvement in the iodide (I-) efflux from thyrocytes remains unclear. Therefore, we examined the effects of ClC-3 on I- efflux. ClC-3 expression was found to significantly alter the serum TT3 and TT4 concentrations in mice. We further found that excess I- stimulation affected ClC-3 expression, distribution, and I- efflux in FRTL-5 cells. Immunofluorescence analyses indicated that ClC-3 mainly accumulated in the cell membrane and co-localized with ß-tubulins after 24â h of excess I- treatment, and that this process depended on ROS production. Thus, ClC-3 may be involved in I- efflux at the apical pole of thyrocytes via excess I--induced ROS production and ß-tubulin polymerization. Our results reveal novel insights into the role of ClC-3 in I- transport and thyroid function.
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Canais de Cloreto/metabolismo , Células Epiteliais da Tireoide , Animais , Transporte Biológico , Iodetos , Camundongos , Prótons , Espécies Reativas de Oxigênio , Tubulina (Proteína)RESUMO
OBJECTIVES: To screen and verify differential genes affecting the prognosis of breast cancer. METHODS: Breast cancer gene expression datasets were downloaded from the GEO database, and original data were analyzed in R. The TIMER database was used to analyze the relationship between ANLN and UBE2T and immune cell infiltration. RESULTS: Ten hub-key genes were identified, and survival analysis showed that UBE2T and ANLN were upregulated in breast cancer and their upregulation was associated with a poor prognosis. ANLN and UBE2T upregulation was associated with the prevalence of Th1 and Th2 cells, shifting the Th1/Th2 balance to Th2 in Basal and Luminal-B breast cancers, which indicates a poor prognosis (P < 0.05). CONCLUSION: ANLN and UBE2T are potential biomarkers for predicting the prognosis of breast cancer.
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The short circulatory half-lives and low tumor accumulation of carboplatin greatly limit the drug's efficacy in vivo. Herein, we address these challenges by using a prodrug strategy and present the rational design of a novel platinum(IV) anticancer prodrug that can hitchhike on erythrocytes. This prodrug, designated as ERY1-PtIV , can bind to erythrocytes efficiently and stably, possessing a circulatory half-life 18.5â times longer than that of carboplatin in mice. This elongated circulatory half-life enables platinum to accumulate at levels 7.7â times higher than with carboplatin, with steady levels in the tumors. As a consequence, the ERY1-PtIV prodrug is proved to exhibit significantly enhanced antitumor activity and reduced side effects compared with carboplatin. Collectively, our novel approach highlights an efficient strategy to utilize intrinsic erythrocytes as auto-binding carriers to enhance the tumor accumulation and subsequent antitumor efficacy of platinum drugs.
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Antineoplásicos , Neoplasias , Pró-Fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carboplatina/farmacologia , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Eritrócitos , Camundongos , Neoplasias/tratamento farmacológico , Platina/uso terapêutico , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêuticoRESUMO
PURPOSE: To compare the clinical results of anterior cruciate ligament (ACL) reconstruction using the single-tunnel single-bundle (STSB) technique versus the single-tunnel double-bundle (STDB) technique. METHODS: This was a retrospective, single-center, single-surgeon study based on data collected from March 2012 to June 2013. According to our inclusion/exclusion criteria, a total of 78 patients (64 males, 14 females; mean age, 25.1 years) who underwent arthroscopic ACL reconstruction with anterior tibialis tendon allografts through either the STSB technique (36 cases) or the STDB technique (42 cases) in our department were recruited. The International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores were used to evaluate the subjective function of the knee joint during the postoperative follow-up. The Lachman test and pivot shift test were used to objectively assess the stability of the knee. RESULTS: The average follow-up duration was 24.9 ± 1.8 months in the STSB group and 24.6 ± 1.7 months in the STDB group (P > 0.05). Patients in both groups recovered to the preoperative sports level with few complications. The postoperative Lysholm score (86.1 ± 7.5 vs. 47.7 ± 9.0 in the STSB group; 87.0 ± 7.1 vs. 48.2 ± 8.3 in the STDB group), IKDC score (87.8 ± 7.2 vs. 49.3 ± 6.1 in the STSB group; 88.7 ± 6.6 vs. 49.8 ± 6.3 in the STDB group), Tegner score (6.5 ± 1.3 vs. 2.5 ± 1.3 in the STSB group; 6.6 ± 1.2 vs. 2.6 ± 1.2 in the STDB group), Lachman test positive rate (8.3% vs. 89.9% in the STSB group; 7.1% vs. 85.7% in the STDB group), and pivot shift test positive rate (27.8% vs. 63.9% in the STSB group; 7.1% vs. 69.0% in the STDB group) were significantly improved compared to the preoperative status in both groups (P < 0.05). However, no statistically significant difference was observed between the two groups at the final follow-up (P > 0.05), except for the pivot shift test positive rate in the STDB group versus the STSB group (7.1% vs. 27.8%, P < 0.05). CONCLUSIONS: The STDB technique achieved a satisfactory clinical outcome with better rotational stability compared to the traditional STSB technique and therefore provided an effective option for ACL reconstruction. LEVEL OF EVIDENCE: Case series, Level IV.
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Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Adulto , Aloenxertos , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/diagnóstico , Lesões do Ligamento Cruzado Anterior/cirurgia , Artroscopia/métodos , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Dendritic cells (DCs) are a cluster of heterogeneous antigen-presenting cells that play a pivotal role in both innate and adaptive immune responses. Rare reports have discussed their role in OA immunopathogenesis. Recently, DCs derived from the synovial fluid of OA mice were shown to have increased expression of toll-like receptors. Moreover, from in vitro studies it was concluded that DCs derived from OA patients had secreted high levels of inflammatory cytokines. Likewise, a significant increase in CD123+BDCA-2 plasmacytoid DCs has been observed in the synovial fluid of OA patients. Furthermore, DCs have a peripheral tolerance potential and can become regulatory under specific circumstances. This could be exploited as a promising tool to eliminate immunoinflammatory manifestations in OA disease. In this review, the potential roles DCs could play in OA pathogenesis have been described. In addition, suggestions for the development of new immunotherapeutic strategies involving intra-articular injections of tolerogenic plasmacytoid DCs for treating OA inflammations have been made.
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Células Dendríticas/imunologia , Gerenciamento Clínico , Imunomodulação , Osteoartrite/terapia , Animais , Citocinas , Humanos , Osteoartrite/imunologia , Osteoartrite/metabolismoRESUMO
Persistent hypotonic and inflammatory conditions in the joint cavity can lead to the loss of cartilage matrix and cell death, which are the important mechanisms of osteoarthritis (OA) onset. Previous studies have confirmed that the existence of a hypotonic environment is a red flag for inflammation, as hypotonic environment induces the opening of the chloride channel of the cell and promotes chloride ion efflux, which prompts the cell volume to increase. Chloride channels play an important role in the regulation of mineralization and chondrocyte death. Here, we reported that OA chondrocytes showed a significant increase of cell death rate and the imbalance of cartilage matrix catabolism. We found that the distribution of skeleton protein F-actin was disordered. In addition, the volume-sensitive chloride current of OA chondrocytes decreased significantly with the increase of the expression levels of inflammation-related proteins caspase-1, caspase-3, and NLRP3. Moreover, interleukin-1ß (IL-1ß) showed a potential to activate the chloride current of normal chondrocytes. These results indicate that IL-1ß-induced chloride channel opening in chondrocytes may be closely related to the occurrence of OA. This chloride channel opening process may therefore be a potential target for the treatment of OA.
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Cloretos/metabolismo , Condrócitos/metabolismo , Interleucina-1beta/metabolismo , Osteoartrite/metabolismo , Idoso , Idoso de 80 Anos ou mais , Condrócitos/patologia , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Transporte de Íons , Masculino , Osteoartrite/patologiaRESUMO
Targeted anticancer prodrugs that can be controllably activated are highly desired for personalized precision medicine in cancer therapy. Such prodrugs with unique action modes are also promising to overcome drug resistance. Herein, we report coumaplatin, an oxaliplatin-based and photocaged Pt(IV) prodrug, to realize nuclear accumulation along with "on-demand" activation. This prodrug is based on a Pt(IV) complex that can be efficiently photoactivated via water oxidation without the requirement of a reducing agent. Coumaplatin accumulates very efficiently in the nucleoli, and upon photoactivation, this prodrug exhibits a level of photocytotoxicity up to 2 orders of magnitude higher than that of oxaliplatin. Unexpectedly, this prodrug presents strikingly enhanced tumor penetration ability and utilizes a distinct action mode to overcome drug resistance; i.e., coumaplatin but not oxaliplatin induces cell senescence, p53-independent cell death, and immunogenic cell death along with T cell activation. Our findings not only provide a novel strategy for the rational design of controllably activated and nucleolus-targeted Pt(IV) anticancer prodrugs but also demonstrate that accumulating conventional platinum drugs to the nucleus is a practical way to change its canonical mechanism of action and to achieve reduced resistance.
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Antineoplásicos/uso terapêutico , Nucléolo Celular/efeitos dos fármacos , Platina/uso terapêutico , Água/química , Antineoplásicos/farmacologia , Humanos , Platina/farmacologiaRESUMO
Extracellular acidification, playing a promoting role in the process of acute pancreatitis, has been reported to activate Cl- channels in several types of cells. However, whether extracellular acidification aggravates acute pancreatitis via activating Cl- channels remains unclear. Here, we investigated the effects of extracellular acidification on Cl- channels in rat pancreatic acinar AR42J cells using whole-cell patch-clamp recordings. We found that extracellular acidification induced a moderately outward-rectified Cl- current, with a selectivity sequence of I- > Br- ≥ Cl- > gluconate-, while intracellular acidification failed to induce the currents. The acid-sensitive currents were inhibited by Cl- channel blockers, 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate and 5-Nitro-2-(3-phenylpropylamino) benzoic acid. After ClC-3 was silenced by ClC-3 shRNA, the acid-sensitive Cl- currents were attenuated significantly, indicating that ClC-3 plays a vital role in the induction of acid-sensitive Cl- currents. Extracellular acid elevated the intracellular level of reactive oxygen species (ROS) significantly, prior to inducing Cl- currents. When ROS production was scavenged, the acid-sensitive Cl- currents were abolished. Whereas, the level of acid-induced ROS was unaffected with silence of ClC-3. Our findings above demonstrate that extracellular acidification induces a Cl- current in pancreatic acinar cells via promoting ROS generation, implying an underlying mechanism that extracellular acidification might aggravate acute pancreatitis through Cl- channels.
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Células Acinares/metabolismo , Canais de Cloreto/metabolismo , Pâncreas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Acinares/citologia , Animais , Linhagem Celular , Cloretos/metabolismo , Espaço Extracelular/metabolismo , Concentração de Íons de Hidrogênio , Pâncreas/citologia , Técnicas de Patch-Clamp , RatosRESUMO
Platinum drugs are widely used in clinics to treat various types of cancer. However, a number of severe side effects induced by the nonspecific binding of platinum drugs to normal tissues limit their clinical use. The conversion of platinum(II) drugs into more inert platinum(IV) derivatives is a promising strategy to solve this problem. Some platinum(IV) prodrugs, such as carboplatin-based tetracarboxylatoplatinum(IV) prodrugs, are not easily reduced to active platinum(II) species, leading to low cytotoxicity in vitro. In this study, we report the design and synthesis of a carboplatin-based platinum(IV) prodrug functionalized with a boron dipyrromethene (bodipy) ligand at the axial position, and the ligand acts as a photoabsorber to photoactivate the platinum(IV) prodrug. This compound, designated as BODI-Pt, is highly stable in the dark but quickly activated under irradiation to release carboplatin and the axial ligands. A cytotoxic study reveals that BODI-Pt is effective under irradiation, with cytotoxicity 11 times higher than that in the dark and 39 times higher than that of carboplatin in MCF-7 cells. Moreover, BODI-Pt has been proven to kill cancer cells by binding to the genomic DNA, arresting the cell cycle at the G2/M phase, inducing oncosis, and generating ROS upon irradiation. In summary, we report a green-light-activatable and carboplatin-based Pt(IV) prodrug with improved cytotoxicity against cancer cells, and our strategy can be used as a promising way to effectively activate carboplatin-based platinum(IV) prodrugs.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos de Boro/química , Carboplatina/química , Corantes Fluorescentes/química , Luz , Pró-Fármacos/química , Carboplatina/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Pró-Fármacos/farmacologiaRESUMO
Evidence has been reported by us and others supporting the important roles of chloride channels in a number of osteoblast cell functions. The ClC-3 chloride channel is activated by estradiol binding to estrogen receptor alpha on the cell membranes of osteoblasts. However, the functions of these chloride channels in estrogen regulation of osteoblast metabolism remain unclear. In the present study, the roles of chloride channels in estrogen regulation of osteoblasts were investigated in the osteoblastic cell line MC3T3-E1. Estrogen 17ß-estradiol enhanced collagen I protein expression, alkaline phosphatase activity, and mineralization were inhibited, by chloride channel blockers. Estradiol promoted ClC-3 chloride channel protein expression. Silencing of ClC-3 chloride channel expression prevented the elevation of osteodifferentiation in osteoblasts, which were regulated by estrogen. These data suggest that estrogen can regulate bone formation by activating ClC-3 chloride channels and the activation of ClC-3 chloride channels can enhance the osteodifferentiation in osteoblasts.
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A high quantum yield (QY) is the key requirement for implementing carbon dots (CDs) in nearly all applications. In this work, blue emissive N-doped CDs with a QY of 83% and orange emissive N-doped CDs with a QY of 47% were successfully prepared using resorcinol and phloroglucin as carbon resources in formamide by one-step microwave synthesis, respectively. Formamide not only plays a role as the solvent but also takes part in the formation of the high QY CDs. It is demonstrated that the as-prepared blue- and orange-emitting N-doped CDs with a high QY can be uniformly dispersed into glue and be fabricated as CD/glue fluorescent composites for fluorescent films and fingerprint imaging. Furthermore, these CDs also show excellent cellular imaging capability.
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Carbono/química , Pontos Quânticos/química , Adesivos/química , Carbono/efeitos da radiação , Carbono/toxicidade , Cor , Dermatoglifia , Fluorescência , Humanos , Células MCF-7 , Membranas Artificiais , Microscopia de Fluorescência , Micro-Ondas , Floroglucinol/química , Pontos Quânticos/efeitos da radiação , Pontos Quânticos/toxicidade , Resorcinóis/química , SolubilidadeRESUMO
Many clinical trials using combinations of platinum drugs and PARP-1 inhibitors (PARPi) have been carried out, with the hope that such combinations will lead to enhanced therapeutic outcomes against tumors. Herein, we obtained seven potential PARPi with structural diversity and then conjugated them with cisplatin-based platinum(IV) complexes. Both the synthesized PARPi ligands and PARPi-Pt conjugates [PARPi-Pt(IV)] show inhibitory effects against PARP-1's catalytic activity. The PARPi-Pt(IV) conjugates are cytotoxic in a panel of human cancer cell lines, and the leading ones display the ability to overcome cisplatin resistance. A mechanistic investigation reveals that the representative PARPi-Pt(IV) conjugates efficiently enter cells, bind to genomic DNA, disturb cell cycle distribution, and induce apoptotic cell death in both cisplatin-sensitive and -resistant cells. Our study provides a strategy to improve the cytotoxicity of platinum(IV)-based anticancer complexes and overcome cisplatin resistance by using a small-molecule anticancer complex that simultaneously damages DNA and inhibits PARP.
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Antineoplásicos/farmacologia , Compostos Organoplatínicos/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Inibidores de Poli(ADP-Ribose) Polimerases/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND Recently, ClC-3 chloride channel expression has been noted to be high in some tumors. In chondrosarcoma, which is a malignant tumor with a high incidence in the bone, there has been no previous literature regarding ClC-3 chloride channel expression. Here we evaluated the expression of ClC-3 chloride channel in chondrosarcoma and explored its clinical significance. MATERIAL AND METHODS In this study, 75 chondrosarcoma and 5 normal cartilage tissues were collected. Thereafter, tissue microarray was performed. Immunohistochemistry was also used to observe the level of ClC-3 chloride channel expression between normal and chondrosarcoma tissues. RESULTS Results showed that the expression of ClC-3 chloride channel in the normal chondrocyte was thinner, since it showed distinct differentiation among chondrosarcoma specimens. Interestingly, we noticed that the moderately-differentiated chondrosarcoma (MDC) and the poorly-differentiated chondrosarcoma (PDC) exhibited 94.44% of ClC-3 chloride channel. Besides, the subcellular localization of ClC-3 chloride channel was changed in association with malignant degree changes. The subcellular localization of ClC-3 chloride channel in the MDC and PDC tissue was localized in the cytoplasm and both nucleus and cytoplasm: 83.33% (5 out of 6 cases) and 91.66% (11 out of 12 cases) respectively. On the other hand, we noticed that patient age and gender could have a relation with ClC-3 chloride channel expression; 30- to 60-year-old males showed more expression. CONCLUSIONS These results demonstrated a high frequency of ClC-3 chloride channel overexpression and subcellular localization differences in MDC and PDC tissue, suggesting a specific role of ClC-3 chloride channel in the pathogenesis of chondrosarcoma.
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Canais de Cloreto/metabolismo , Condrossarcoma/metabolismo , Análise Serial de Tecidos , Adolescente , Adulto , Fatores Etários , Diferenciação Celular , Linhagem Celular Tumoral , Condrossarcoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Adulto JovemRESUMO
Three kinds of carbon dots (CDs) with different photoluminescence (PL) (blue, yellow or orange) were synthesized by microwave heating. They display wavelength-independent excitation wavelengths (in the range from 444 to 574 nm), similar average particle size (from 3.7 to 4.2 nm), and fluorescence lifetimes (from 2.7 to 3.1 ns). Color and quantum yields (from 8 to 45% in ethanol) are related to the oxidation degree and the number of N-functional groups on their surface. The CDs are shown to be viable nanoprobes for multicolor imaging of cells. Three composite phosphors were obtained by coating the various CDs on starch particle. The resulting nanomaterials emit solid-state fluorescence with a quantum yield of ≥16%. They were used to fabricate luminescent blocks and light-emitting diodes with controllable color temperature. Graphical abstract (a) The synthesis process of the three carbon dots (CDs). The application in cell imaging (b), starch/CD phosphors (c), starch/CD phosphors-based luminescent blocks (d) and light-emitting diodes (e). (λex: excitation wavelength).
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Estrogen plays important roles in regulation of bone formation. Cl- channels in the ClC family are expressed in osteoblasts and are associated with bone physiology and pathology, but the relationship between Cl- channels and estrogen is not clear. In this study the action of estrogen on Cl- channels was investigated in the MC3T3-E1 osteoblast cell line. Our results show that 17ß-estradiol could activate a current that reversed at a potential close to the Cl- equilibrium potential, with a sequence of anion selectivity of I- > Br- > Cl- > gluconate, and was inhibited by the Cl- channel blockers 5-nitro-2-(3-phenylpropylamino)-benzoate and 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid. Knockdown of ClC-3 Cl- channel expression by a specific small interfering RNA to ClC-3 attenuated activation of the 17ß-estradiol-induced Cl- current. Extracellular application of membrane-impermeable 17ß-estradiol-albumin conjugates activated a similar current. The estrogen-activated Cl- current could be inhibited by the estrogen receptor (ER) antagonist fulvestrant (ICI 182780). The selective ERα agonist, but not ERß agonist, activated a Cl- current similar to that induced by 17ß-estradiol. Silencing ERα expression prevented activation of estrogen-induced currents. Immunofluorescence and coimmunoprecipitation experiments demonstrated that ClC-3 Cl- channels and ERα were colocalized and closely related in cells. Estrogen promoted translocation of ClC-3 and ERα to the cell membrane from the nucleus. In conclusion, our findings show that Cl- channels can be activated by estrogen via ERα on the cell membrane and suggest that the ClC-3 Cl- channel may be one of the targets of estrogen in the regulation of osteoblast activity.
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Canais de Cloreto/genética , Receptor alfa de Estrogênio/genética , Estrogênios/metabolismo , Osteoblastos/metabolismo , Animais , Membrana Celular/genética , Membrana Celular/metabolismo , Canais de Cloreto/antagonistas & inibidores , Canais de Cloreto/biossíntese , Estradiol/administração & dosagem , Receptor alfa de Estrogênio/metabolismo , Camundongos , Osteogênese/genéticaRESUMO
STUDY QUESTION: Is chloride channel-3 (ClC-3) involved in regulating the biological behavior of endometrial stromal cells (ESCs)? SUMMARY ANSWER: ClC-3 promotes endometriotic cell migration and invasion. WHAT IS KNOWN ALREADY: ClC-3 plays a significant role in the migration and invasion of various kinds of cells. STUDY DESIGN, SIZE, DURATION: An ITALIC! in vitro investigation of the effect of ClC-3 on the migration and invasion of ectopic ESCs from patients with endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The ectopic and eutopic endometrial samples from 43 female patients with endometriosis and the endometrial samples from 39 non-endometriotic female patients were collected. Primary cells from these samples were isolated and cultured. Real-time RT-PCR, immunohistochemistry and western blot were used to detect the expression of ClC-3 and matrix metalloproteinase 9 (MMP-9). Small interfering RNA (siRNA) technology was employed to knock down ClC-3 expression. The migration and invasion ability of ESCs was measured by the transwell assay with uncoated or Matrigel-coated membranes. MAIN RESULTS AND THE ROLE OF CHANCE: The expression of ClC-3 mRNA and proteins was significantly up-regulated in the ectopic tissues from endometriotic patients, while that in the eutopic endometrial tissues of the same patients did not significantly differ from that in non-endometriotic patients. The migration and invasion ability and MMP-9 expression was increased in the ESCs from ectopic endometrial tissues. The knockdown of ClC-3 expression by ClC-3 siRNA inhibited ESC migration and invasion and attenuated the expression of MMP-9. ClC-3 expression level was well-correlated to the clinical characteristics and symptoms of endometriosis patients, including infertility, dysmenorrhea, chronic pelvic pain, dyspareunia and diameter of endometriosis lesion. LIMITATIONS, REASONS FOR CAUTION: Further studies are needed to examine the regulatory mechanism of estrogen on ClC-3 expression of ESCs. WIDER IMPLICATIONS OF THE FINDINGS: ClC-3 is involved in the migration and invasion processes of ESCs and can regulate MMP-9 expression. Up-regulation of ClC-3 expression may contribute to endometriosis development by regulating MMP-9 expression. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (81173064, 81272223, 81273539), the Ministry of Education of China (20124401110009), the Natural Science Foundation of Guangdong Province (S2011010001589) and the Science and Technology Programs of Guangdong (2013B051000059), Guangzhou (2013J500015) and Dongguan (2011108102006). The authors have no conflict of interest.
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Movimento Celular/genética , Canais de Cloreto/metabolismo , Endometriose/genética , Técnicas de Cultura de Células , Células Cultivadas , Canais de Cloreto/antagonistas & inibidores , Canais de Cloreto/genética , Endometriose/metabolismo , Endometriose/patologia , Endométrio/citologia , Endométrio/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Interferência de RNA , Células Estromais/citologia , Células Estromais/metabolismo , Regulação para CimaRESUMO
The aim of this study was to investigate the relationship between the acetylcholine concentration in the blood and gelsenicine-induced death in mice. Kunming mice were given intraperitoneal injections of normal saline, gelsenicine or different doses of acetylcholine chloride. Atropine was given to the mice which received gelsenicine or medium dose acetylcholine chloride injection. The blood was sampled immediately when the mice died or survived for 20 min after injection. The acetylcholine concentration and acetylcholinesterase activity in the blood were measured by the testing kits, and the mortality was calculated and analyzed. The results showed that half lethal dose of gelsenicine (0.15 mg/kg) reduced the acetylcholinesterase activity and increased the blood acetylcholine concentration. The blood acetylcholine concentration of the dead mice in the gelsenicine group was increased to 43.0 µg/mL (from 31.1 µg/mL in the control), which was lower than that (53.9 µg/mL) of the dead mice in the medium dose acetylcholine chloride group, but almost equal to that (42.7 µg/mL) of the survival mice in the medium dose acetylcholine chloride group. Atropine could successfully rescue the mice from acetylcholine poisoning, but its efficiency of rescuing the mice from gelsenicine intoxication was weak. These results suggest that gelsenicine can inhibit acetylcholinesterase activity and increase blood acetylcholine concentration, but the accumulation of acetylcholine may not be the only or main cause of the death induced by gelsenicine in mice.
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Morte , Acetilcolina , Animais , Alcaloides Indólicos , CamundongosRESUMO
The mitochondrion, one of the important cellular organelles, has the major function of generating adenosine triphosphate and plays an important role in maintaining cellular homeostasis, governing signal transduction, regulating membrane potential, controlling programmed cell death and modulating cell proliferation. The dynamic balance of mitochondrial volume is an important factor required for maintaining the structural integrity of the organelle and exerting corresponding functions. Changes in the mitochondrial volume are closely reflected in a series of biological functions and pathological changes. The mitochondrial volume is controlled by the osmotic balance between the cytoplasm and the mitochondrial matrix. Thus, any disruption in the influx of the main ion, potassium, into the cells can disturb the osmotic balance between the cytoplasm and the matrix, leading to water movement between these compartments and subsequent alterations in mitochondrial volume. Recent studies have shown that mitochondrial volume homeostasis is closely implicated in a variety of diseases. In this review, we provide an overview of the main influencing factors and research progress in the field of mitochondrial volume homeostasis.
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Canais Iônicos , Dinâmica Mitocondrial , Tamanho Mitocondrial , Canais Iônicos/metabolismo , Mitocôndrias/metabolismo , Transdução de SinaisRESUMO
TMEM16 proteins, which function as Ca2+activated Cl channels are involved in regulating a wide variety of cellular pathways and functions. The modulators of Cl channels can be used for the moleculebased treatment of respiratory diseases, cystic fibrosis, tumors, cancer, osteoporosis and coronavirus disease 2019. The TMEM16 proteins link Ca2+ signaling, cellular electrical activity and lipid transport. Thus, deciphering these complex regulatory mechanisms may enable a more comprehensive understanding of the physiological functions of the TMEM16 proteins and assist in ascertaining the applicability of these proteins as potential pharmacological targets for the treatment of a range of diseases. The present review examined the structures, functions and characteristics of the different types of TMEM16 proteins, their association with the pathogenesis of various diseases and the applicability of TMEM16 modulatorbased treatment methods.